Preparation of multifunctional nanoparticles using microfluidics

Abstract

Liposomes have been the most successful drug delivery nanosystems for clinical applications; however, their large-scale production with low batch-to-batch variations remains challenging, which limited the clinical translation of new products. Microfluidics is an emerging technology for manipulating and controlling fluids at microscale. Compared to conventional batch reactors, microfluidics has shown great promise for the production of liposomes, offering simpler operations with improved reproducibility and scalability.

The present thesis focuses on engineering multifunctional liposomes using microfluidics. Firstly, conventional sterically stabilised liposomal formulations were prepared by microfluidic-assisted nanoprecipitation. The effect of processing and formulation parameters were studied, and the physicochemical properties of the prepared liposomes were determined. It was shown that the processing parameters: total flow rate (TFR), and aqueous-to-organic phase flow rate ratio (FRR), can effectively control liposome size. However, optimisation of formulation parameters was necessary for particular liposomal formulations where the engineered liposomes were heterogeneous regardless of the processing parameters (or liposome size). Secondly, microfluidic production of lysolipid-containing thermosensitive liposomes (LTSL) was investigated. Modification of formulation parameters was required to avoid ethanol-induced interdigitation. Upon increasing PEG-lipid content in the formulation, homogeneous LTSL were successfully prepared. Thirdly, microfluidic production of fluorescent dye indocyanine green (ICG)-loaded liposomes was studied for potential imaging and photothermal applications. Lastly, encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPION) into LTSL was explored for their theranostic applications. Solvent compatibility of the microfluidic device was shown to be a limiting factor, which necessitated modifications of the preparation technique. Nanoprecipitation of SPION-loaded LTSL was successfully demonstrated by optimisation of the solvent system and concentration of SPION. This thesis demonstrated the capability of microfluidics in preparing multifunctional liposomes, enabling their continuous and scalable production.

Date of Award	Dec 2020
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Wafa Al-Jamal (Supervisor) & Colin McCoy (Supervisor)